Muscle fiber shortening in the complex fiber architecture of the left ventricle is converted into an efficient coordinated ventricular contraction. Studies that span several decades have addressed the problem of how local myofiber contraction contributes to changes in cavity volume. ONly recently have quantitative approaches to this problem been developed which measure three-dimensional deformations and their directions with sufficient resolution to relate local deformation to local myofiber anatomy. These studies have shown that in the left ventricular free wall the orientation of the first principal axis of strain (direction of greatest shortening) does not vary transmurally nearly as much as the fiber direction. This implies that there is substantial shortening perpendicular to the local fiber direction during contraction. In the present there is substantial shortening perpendicular to the local fiber direction during contraction. In the present proposal, we will continue to explore the hypothesis that relative myofiber position or shape changes of the myocyte or interstitium during contraction account for these cross-fiber strains. The normal electrical activation of the left ventricle, initiated from the atrium and traveling through the His-Purkinje system via the atrioventricular node, provides for relatively synchronous activation of ventricular muscle. Most current information indicates that with ventricular activation the relationship between mechanical activity and activation is much more complex. iN the present proposal, we plan to use a newly developed technique for fitting surfaces to activation times, and to arrays of implanted markers to determine spatial gradients of deformation. Changes in myocardial strain in the presence of volume overload have classically been considered a passive response to the abnormalities of ventricular loading conditions. More recent studies, however, have indicated that these changes in strain may directly transduce the signal to compensatory hypertrophy, with ultimate normalization of wall stress as a consequence. Through the regulation of cell growth, changes in regional strain may ultimately alter, as well as reflect, local loading parameters. The acute onset of volume overload induces large increases in both muscle and nonmyocytic constituents of the myocardium. In this study, we propose (1) to examine the time course of the changes in transmural function of the myocardium as hypertrophy occurs, and (2) to correlate the time course of changes in systolic and diastolic finite strains with the time course of increases and decreases in mRNA levels for ANF, alpha-skeletal actin, MLC2, HSP, fibronectin, and collagen. Our approach will have several advantages over those previously used to examine the relationship between changes in function and hypertrophy of cardiac muscle. First, finite deformation may be assessed n any arbitrary reference system. With knowledge of the local myofiber anatomy this will allow the examination of deformation in the direction of local fibers and in the cross-fiber direction. This should then allow a more direct assessment of the local mechanical stimulus to increased protein synthesis, and of the mechanical effects of increased contractile and extracellular protein. Second as discussed in the preliminary results, the implanted markers will allow us to identify small volumes of muscle across the wall and to track changes in volume during the progression of hypertrophy. This will allow us to test repeatedly for transmural differences in the amount of hypertrophy.